Presentation on theme: "Can We Preserve The Bladder In Muscle Invasive Bladder Cancer?"— Presentation transcript:
1 Can We Preserve The Bladder In Muscle Invasive Bladder Cancer? Dr Manish PatelUrological Cancer SurgeonWestmead HospitalUniversity of Sydney
2 The Outcomes of Radical Cystectomy Outcomes of RC are very good.Recurrences occur:Median 12 months86% of recurrences occur in first 3 years.Local only recurrence more likley in OC.Most series- any recurrence= death.Even with LN+ve disease, 30% likelihood of long term survival.Stein et.al. Journal of Clinical Oncology, Vol 19, No 3 (February 1), 2001: pp
3 Upstaging is common with Bladder Cancer Based on TURBT, EUA, CTMRI with dynamic contrast enhancement and Fe particles may be better.Ureteric obstruction- 67%-90% >pT2 (Skinner et,al,1998)Muscle invasive bladder cancer (cT2) is upstaged to pT3 in:52% (Soloway et.al.1994)78% (Pagano et.al.1991)41% (Frazier et.al.1992)Most cT2 bladder cancers are pT3 or higher.Occult LN mets increase with increasing P stageP0, Pa, Pis, P1: 5%P2: %P3-4: 45%
4 Quality of Life After RC is Good. There are a number of QoL instruments for bladder cancer.Very few reports on QoL after BC treatment.Lack of baseline measurements.Lack of longitudinal measurements.No comparison of RC vs Bladder Preservation.Only on prospective QoL study (SF-36) (Hardt et.al)Physical functioning decreased pre-post-op (80 to 68)Pain, health perception, vitality, social functioning, general well being, satisfaction with life all the same as pre-op at one year.
5 Options of Bladder Preservation with Muscle Invasive BC TURBT alonePartial Cystectomy aloneExternal Beam Radiation AloneBrachytherapyNeoadjuvant Chemo and TURBTNeoadjuvant Chemo and Partial cystectomyMultimodality therapy
6 Does a delay in cystectomy Result in lower survival? Randomised studies of immediate cystectomy vs XRT and salvage cystectomy.StudyRandomised groupsSurvivalMD Andersen (n=67)Immediate XRT+cystectomy5yrs: 45%XRT and salvage cystectomy5yrs: 22%Urologic Co-operative Group UK (n=187)Immediate cystectomy5 yrs: 39%XRT with salvage surgery5 yrs: 29%Danish National Bladder Group (n=187)5 yrs: 23%Possibly: Need low threshold for salvage cystectomy
7 TURBT Author Protocol Survival Cystectomy rate Barnes (n=85) G1/2 T2 TURBT X127% 5 yrsHenry (n=43)Favourable (small T2) TURBT X177% 5 yrs25%Solsona (n=59)Negative cytology and rpt biopsyyrs19%Herr (n=45)Negative rpt TUR and cytology5 yrs24%TURBT is feasible for selected T2 bladder tumours.Not for dome or high posterior wall
8 Partial Cystectomy MSKCC study (contemporary) 85 patients with T2 OS: 5yrs74% alive with bladder intact67% alive with NED bladder intact7 pts sup recurrence15 pts advanced recurrence75% false negative frozen section margins.80% of positive margins suffered advanced recurrence.Selection:Dome/post wall/diverticulum
9 Partial Cystectomy Candidates: CR or PR to Neoadjuvant chemo Solitary lesions in favoyrable locationsNo CISGood bladder capacity.
10 Radiation TURBT and 65 Gy XRT StudyPatient no.Survival (5 yr%)T2T3Fossa et.al.3083814Davidson et.al7094928Gospodarowicz3555032Goffinet et.al.3844235TURBT and 65 Gy XRTTumour debulking (TURBT may be most important)Assessment of response at 40Gy may be usefulCR to XRT- will have a good outcome.60% invasive recurrence rate. Approx 50% cystectomy rate.Co-existant CIS: High recurrence rate in bladder (70%).Squamous differentiation may have poorer outcome
11 Radiation-Complications Early complicationsDiarrheaBladder irritation (particularly if trigonal cancers)Late complications (2-3 years later)Worse if heavily pretreated (TURBTS, BCG etc)Radiation cystitis (heamturia, frequency contracted bladder)Radiation proctitis (persistent diarrhea, rectal bleeding)Sexual dysfunction (60%)Tumour RecurrenceInvasive – salvage cystectomySuperficial- as per normal protocols
12 Neoadjuvant and Partial cystectomy Neoadjuvant chemotherapy (X3-4 cycles) followed by TURBT staging.Then followed by partial cystectomy and pelvic lymph node dissection.Herr et.al (n=26). No Pt was eligible for PC alone.19 had P07 yr median FU: 65% alive54% with bladder18% invasive recurrence26% superficial recurrencePC is a valid option in suitable patients, even with T3 tumours that are small.
13 Neoadjuvant and TURBT Neoadjuvant chemo (3-4 cycles). Restaging TURBT. Stenberg et.al (n=71). T2-T4aMedian 54 months FU: 71% alive57% bladder intactAfter chemo: P0 or superficial disease, 5yr survival = 71%Invasive disease 29%MSKCC (n=111)60(54%) achieved T0 status.- Most preserved bladders56% recurrence in bladder (30% invasive)25% of T0 is not P0.
14 Neoadjuvant chemotherapy and TURBT Srougi et.al. (n=30)TURBT, MVACX3.PR or no response > cystectomy (n=12)CR > all retained their bladder (n=14)5 yrs, 71% (10) had local recurrences.8 had radical cystectomySurvival of all CR pts was 5yrs.All patients need close observation because of inadequate staging and occurrence of new tumours.
15 Trimodality Therapy Maximal TURBT XRT Concurrent chemotherapy Rational Cisplatin, 5-FU and paclitaxel sensitise tumour tissues to XRT.Increase cell kill in a synergisitic fashion.Also high (25%-50%) chance of micro-metastatic disease at presentation.
16 Trimodality TherapyDoes the radiation add anything, as XRT outcomes are similar to TURBT outcomes?SeriesTreatment5 yr survival5 yr survival with bladderTURBT, XRT and concurrent Chemotherapy.Dunst (n=79)TURBT, cisplatin, XRT52%41%RTOG 1993 (n=42)Cisplatin and XRT42%Kachnic (n=106)TURBT, MCV and XRT43%RTOG 1997 (n=123)49%38%TURBT and Chemotherapy aloneGiven (n=93)TURBT and MCV51%18%Srougi (n=30)Partial C and MVAC53%20%It appears that concurrent chemo/XRT does add something.
17 Shipley- Massachusetts General Protocol Hydronephrosis, Poor renal function Irritable bladder, Low Capacity T4a/4b, CISIf no, Maximal TURBTIf yes, For surgeryNo SignificantTumour RemainingBulkyTumour RemainingChemo/ XRTProtocol-InductionCE 4 weeks after inductionRadicalCystectomyCR, consolidationChemoradiationResidual Cancer
18 MGH- Chemoradiation Protocol Induction2 cycles of neoadjuvant MCVMethotrexate, cisplatin, vinblastineConcurrent cisplatin and 40Gy XRTConsolidation chemoradiationFurther 24Gy XRTCisplatin based chemotherapy
19 MGH- Results Patients selected for Trimodality therapy (n=190) Denominator unknownInduction chemotherapy29 (15%) had residual disease > RC40 (21%) unable to tolerate ChemoRad > RC121 (64%) went on to have consolidation Chemoradiation.After 4 years median FU86 (45%) alive with NED110 (58%) still had a bladder.Overall 5 yrs 54%
20 RTOG bladder sparing protocols All tumours are small.All tumours are able to be maximally resected.These are not the same tumours in cystectomy series.All patients are healthy with good ECOG statusAll patients were eligible for cystectomy.
21 Clinical Preictors of Outcome Stage (cT2=62%, cT3=47%)Hydronephrosis (CR= 37% vs 68%)CR on induction chemoradiationQuality of LifeCystectomy for bladder contracture (2-7%)On going urinary symptomsWomen-19% incontinenceReduced urinary compliance in 22%Bowel symptoms- 22%Sexual dysfunction
22 Concerns with Bladder sparing therapy Need for complete TURBT (visibly clear)CR 77% vs 54% for visble and not visible complete resection.Survival 52% vs 5 yrsUrothelial cancer changeThose with CR to trimodality will develop20-30% new or recurrent bladder tumorOccur median of 2.1 years and mainly CISUltimately 1/3 of recurrence need late cystectomy.Pelvic recurrence12%Delay in cystectomyLimited diversion alternatives.
23 Is Bladder Preservation Equivalent to Radical Cystectomy? No but!Viable alternative for Pts wanting to preserve bladderOnly small likely decrease in survivalButNot all patients are suitable50% will ultimately have cystectomyDiversion choices will be limited.Operation more difficult and complications higher.Not evidence that quality of life is actually better.A number of pts will have significant bladder and bowel symptoms.